Coordinated development requires that growth and cell-fate transitions occur in a defined temporal order across tissues, yet how multicellular organisms generate and synchronize developmental timing information remains unclear. In Caenorhabditis elegans , stage-specific cell-fate transitions are driven by pulsatile transcription of microRNAs, including lin-4 and let-7 family members, but the mechanism that produces these rhythms has been unknown. Here, we identify a developmental timer composed of the transcription factor MYRF-1 and the PERIOD-like repressor LIN-42 that operates synchronously across all somatic tissues. MYRF-1 binds conserved regulatory elements upstream of heterochronic microRNA genes and drives once-per-stage transcriptional pulses that are phase-locked across tissues, while simultaneously activating lin-42 expression. Newly synthesized LIN-42 directly associates with MYRF-1, limiting its nuclear residence and transcriptional activity and thereby constraining the amplitude and duration of each pulse. Beyond regulating stage-specific gene expression, we show that MYRF-1 activity is also required to license a developmental checkpoint essential for growth and successful ecdysis. Together, these findings define a reciprocal transcriptional–translational feedback loop that generates organism-wide developmental timing information, coupling tissue-specific differentiation programs to coordinated organismal growth through a shared molecular timer.
Building similarity graph...
Analyzing shared references across papers
Loading...
Peipei Wu
Jing Wang
Brett Pryor
Proceedings of the National Academy of Sciences
New York University
Rockefeller University
Cold Spring Harbor Laboratory
Building similarity graph...
Analyzing shared references across papers
Loading...
Wu et al. (Wed,) studied this question.
www.synapsesocial.com/papers/69fd7f86bfa21ec5bbf080bd — DOI: https://doi.org/10.1073/pnas.2606846123
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: